Background Preterm birth accounts for approximately 11% of all livebirths globally. Due to improvements in perinatal care, more than 95% of these infants now survive into adulthood. Research has indicated a robust association between prematurity and increased cardiovascular risk factors and cardiovascular mortality. While the innate adverse effects of prematurity on these outcomes have been demonstrated, therapeutic strategies on the mitigation of these concerning developments are lacking. The primary objective of the NEOVASC clinical trial is therefore to investigate whether the administration of a prolonged exclusive human-milk diet in preterm infants is capable of alleviating the harmful effects of preterm birth on the early development of cardiovascular risk factors. Methods The NEOVASC study is a multicentric, prospective, randomized, controlled, open, and parallel group clinical trial conducted in four Austrian tertiary neonatal care facilities. The purpose of the present trial is to investigate the effects of a prolonged exclusive human-milk-diet devoid of bovine-milk-based food components on cardiovascular and metabolic risk factors at 1, 2, and 5 years of corrected age. Primary outcomes include assessments of fasting blood glucose levels, blood pressure levels, and the distensibility of the descending aorta using validated echocardiographic protocols at 5 years of corrected age. The test group, which consists of 200 preterm infants, will therefore be compared to a control group of 100 term-born infants and a historical control group recruited previously. Discussion Given the emerging implications of an increased cardiovascular risk profile in the potentially growing population of preterm infants, further research on the mitigation of long-term morbidities in formerly preterm infants is urgently warranted. Further optimizing preterm infants’ nutrition by removing bovine-milk-based food components may therefore be an interesting approach worth pursuing. Trial registration ClinicalTrials.gov NCT04413994. Registered on 4 June 2020.

Background: The first and well replicated childhood asthma susceptibility locus identified by genome-wide association was 17q21. ORMDL3 , located near the top association signal, belongs to the ORMDL gene family including ORMDL1, -2 and -3 . ORMDL proteins participate in the sphingolipid metabolism and maintain the ceramide homeostasis.ORMDL3 regulates the intracellular Ca 2+ levels, cellular stress responses and lymphocyte activation. Strong sequence homology between ORMDL s and protein conservation among different species suggest that they may have shared functions. Objectives: We hypothesized that single nucleotide polymorphisms (SNPs) in ORMDL genesare associated with asthma and that expression of ORMDL s correlates with asthma. Methods: Associations of 44 genotyped SNPs (Illumina HumanHap300Chip, MALDI-TOF MS) were assessed in 1,303 subjects (651 asthmatics) from MAGIC and ISAAC II studies. Expression in: (1) peripheral blood mononuclear cells (PBMC) (n=55, 8 asthmatics) before and after (48h) allergen stimulation; and (2) blood (n=60, 5 asthmatics) was determined. Allele-specific effects on the ORMDL s expression were evaluated. Results: Sixteen SNPs in all three ORMDL genes were associated with asthma (most in ORMDL3 ). Baseline expression in PBMC was significantly higher in asthmatics for ORMDL1 ( p =1.7*10 -6 ) and -2 ( p =4.9*10 -5 ) while induction of ORMDL s upon stimulation was stronger in unaffected subjects. Asthma associated rs8079416 and rs8076131 influenced ORMDL3 expression in allele-specific manner. Conclusions: SNPs in all three ORMDL s are associated with asthma. Asthmatics exhibit increased ORMDL levels, suggesting that ORMDL s contribute to asthma development. These authors contributed equally: Antoaneta Toncheva, Daniel Potaczek and Michaela Schedel.

Canavan disease, an autosomal recessive inherited leukodystrophy caused by an aspartoacylase deficiency, is common among children of Ashkenazi Jewish descent. We report on a non-Jewish female infant who presented at age 6 months with progressive macrocephaly and developmental delay. A sequence analysis of the aspartoacylase gene revealed compound heterozygosity for a known mutation and for the mutation c.432G>A in exon 2, which has not yet been described in Canavan disease.

Neonatal diabetes mellitus (NDM) is a rare condition (1:400,000 neonates) defined as hyperglycemia occurring in the first months of life, lasting more than 2 wk and requiring insulin for management. We here report on a 33-month-old girl with pancreatic agenesis, an extremely rare cause of permanent neonatal diabetes mellitus (PNDM). Timely diagnosis and adequate treatment of both endocrine and exocrine insufficiency may permit survival and normal development.

Our objective was to study how invasive mechanical ventilation impairs cardiac output (CO) in children and adults. Although the application of continuous positive airway pressure (CPAP) is widely practiced in neonatal intensive care, its hemodynamic consequences have not yet been investigated. A prospective study to assess the hemodynamic effects was conducted in 21 preterm infants < 1500 g using two-dimensional M-mode and pulsed Doppler echocardiography during and 1 hour after discontinuation of nasal CPAP (n-CPAP). Gestational age was 28.0 +/- 1.9 weeks (mean +/- standard deviation); birthweight, 1000 +/- 238 g; age at study entry, 200 +/- 155 hours; total maintenance fluid, 154 +/- 42 mL/kg/day; and n-CPAP level, 4.4 +/- 0.9 cm H(2)O. None of the infants received inotropic support, and n-CPAP did not cause any significant difference in the parameters measured: stroke volume, 3.1 +/- 1.0 mL (with n-CPAP) versus 3.1 +/- 1.0 mL (without n-CPAP); cardiac output, 487 +/- 156 mL/minute versus 500 +/- 176 mL/minute; left ventricular diastolic diameter, 1.22 +/- 0.15 cm versus 1.24 +/- 0.14 cm; fractional shortening, 0.30 +/- 0.05% versus 0.29 +/- 0.04%; and aortic velocity-time integral, 8.64 +/- 1.80 cm versus 8.70 +/- 1.65 cm. The n-CPAP level did not influence CO; n-CPAP (up to 7 cm H (2)O) has no echocardiographically detectable hemodynamic effect in preterm infants. Our data imply there is no need to withhold n-CPAP support to prevent circulatory compromise in these infants.

Familial hemophagocytic lymphohistiocytosis (FHL) is a rare, fatal disorder of early infancy. We report two siblings with FHL whose symptoms were dominated by hepatic failure. Both presented with sudden-onset fever and hepatosplenomegaly with progressive abnormalities of clinical biochemistry indices of liver function. One died of hepatorenal failure. The other underwent liver transplantation. Autopsy and explant liver displayed portal and periportal infiltrates of T lymphocytes and histiocytes; an activation of the hepatic mononuclear phagocytic system with focal hemophagocytosis; and almost complete loss of interlobular bile ducts. Paucity of bile ducts dominated in a pre-transplant liver biopsy specimen (and transiently obscured the diagnosis of FHL). Disease recurred in the allograft, again with lymphohistiocytic infiltration and destruction of interlobular bile ducts. Consequently the patient underwent haploidentical peripheral stem cell transplantation. This patient is alive 5 years later. Loss of bile ducts may be an important feature of hepatic involvement by FHL.

Lymphedema-cholestasis syndrome (LCS, Aagenaes syndrome) is the only known form of hereditary lymphedema associated with cholestasis. A locus, LCS1, has recently been mapped to chromosome 15q in a Norwegian kindred. In a consanguine Serbian Romani family with a neonate who had a combination of lymphedema and cholestasis with features atypical for Norwegian LCS, haplotype and linkage analysis of markers spanning the LCS1 region argue that a second LCS locus may exist. The infant may represent an instance of a previously undescribed lymphedema-cholestasis syndrome.

We describe the case of a 22-month-old boy with developmental and psychomotor retardation as well as craniofacial dysmorphism, including a cleft lip. Analysis of G-banded chromosomes of the propositus showed a de novo interstitial deletion of the short arm of chromosome 3, del(3)(p13p11). Fine mapping of the deletion was performed using fluorescence in situ hybridisation analysis with region-specific BAC clones. Eight BACs were absent from one chromosome 3 from the patient. Molecular analyses of eleven polymorphic DNA markers helped to narrow down the breakpoints and demonstrated that the derivative chromosome 3 is of paternal origin. The deleted segment encompasses about 15 Mb between marker D3S3551 and the centromere. Only a small number of known genes, including PROK2, GPR27, RYBP, PPP4R2, ROBO1, and GBE1, which map in the 3p13-p11 region are included in the deletion.